Megakaryocyte volume modulates bone marrow niche properties and cell migration dynamics.

Abstract:

:All hematopoietic cells that develop in the bone marrow must cross the endothelial barrier to enter the blood circulation. Blood platelets, however, are released by bigger protrusions of huge progenitor cells, named megakaryocytes, and enter the blood stream as so-called proplatelets before fragmenting into mature platelets. Recently, a second function of megakaryocytes has been identified, as they modulate the quiescence of hematopoietic stem cells, mostly via different soluble factors. We know from light sheet fluorescence microscopy images that megakaryocytes are distributed throughout the bone marrow facing a dense vascular network. Here, we used such three-dimensional images to provide a realistic simulation template reflecting the in vivo cell-vessel distributions resulting in reliable whole-bone analysis in silico Combining this approach with an automated image analysis pipeline, we found that megakaryocytes influence migration of neutrophils and hematopoietic stem cells, and thus act as biomechanical restrainers modulating cell mobility and extravasation. Indeed, as a consequence of increased megakaryocyte volumes in platelet-depleted mice neutrophil mobility was reduced in these animals.

journal_name

Haematologica

journal_title

Haematologica

authors

Gorelashvili MG,Angay O,Hemmen K,Klaus V,Stegner D,Heinze KG

doi

10.3324/haematol.2018.202010

subject

Has Abstract

pub_date

2020-04-01 00:00:00

pages

895-904

issue

4

eissn

0390-6078

issn

1592-8721

pii

haematol.2018.202010

journal_volume

105

pub_type

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